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Accession Number:
AD1023980
Title:
Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease
Descriptive Note:
Technical Report,01 Sep 2015,31 Aug 2016
Corporate Author:
Yale University New Haven United States
Report Date:
2016-09-01
Pagination or Media Count:
20.0
Abstract:
Autosomal dominant polycystic kidney disease ADPKD is a common inherited disorder where patients, over the course of decades, develop large fluid filled cysts that damage the normal kidney tissue and can lead ultimately to kidney failure that necessitates transplantation or dialysis. There are currently no FDA-approved medications for this condition. Recent research reveals that the formation of cysts is due in part both to inappropriate cell growth, fluid secretion, and dysregulation of cellular energy metabolism. The enzyme AMPK regulates a number of cellular pathways, including these disease-causing features. Drugs that activate AMPK, therefore, may constitute an effective therapeutic option for slowing or preventing cyst growth in ADPKD. This research project is aimed at examining the potential of approved, widely used, inexpensive and low-toxicity drugs that can activate AMPK metformin, simvastatin, and salicylates and or promote oxidative metabolism dichloroacetic acid as potential therapies for the treatment of ADPKD. During this past research period, we optimized the measurement and analysis of various metabolites and metabolic enzymes metabolomic biomarkers in samples derived from cell lysates and urine and collected preliminary data in ADPKD mouse in vitro cell culture models and urine specimens derived from a cross-section of patients with ADPKD.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
